109 - Effectiveness of High vs. Standard Dose Ibuprofen for Late Treatment of Patent Ductus Arteriosus (PDA) Among Extremely Low Gestational Age Neonates (ELGANs)

Poster Number: 109
Publication Number: 109.1849

Background: Ibuprofen is commonly used as a pharmacological treatment for hemodynamically significant PDA, however, there is uncertainty regarding the optimal dose for late treatment (after Day 7). Owing to increasing clearance of ibuprofen over the first week, pharmacokinetic studies support the use of a high-dose (HD, 20-10-10 mg/kg) compared with a standard-dose regimen (STD, 10-5-5 mg/kg). While clinical trials have demonstrated increased efficacy of a HD regimen among more mature preterm neonates, there is a paucity of data on effectiveness among ELGANs (gestational age [GA] < 28 weeks) for late PDA treatment.

Objective: Evaluate the association of HD vs. STD ibuprofen for PDA with treatment success and neonatal outcomes among ELGANs.

Design/Methods: Retrospective comparative epoch study of ELGANs treated with ibuprofen for hsPDA after Day 7 at two tertiary perinatal centres. Neonates in epoch 1 (01/2016–06/2019) received STD ibuprofen while neonates in epoch 2 (07/2019–12/2021) received HD ibuprofen. The primary outcome was effectiveness in inducing PDA closure, defined as ≥ 25% reduction in PDA diameter. Secondary outcomes included neonatal mortality and major morbidity and time to wean off of mechanical ventilation. Multivariable logistic regression analysis was used to evaluate the association between treatment dose and outcomes, adjusting for PDA diameter and clinical and echocardiographic confounders. Time to weaning off of mechanical ventilation was evaluated using Cox proportional hazard analysis.

Results: One hundred fifty-six ELGANs (mean[SD] GA 24.6 [±1.2] weeks, birthweight 686 [±160]g) received late PDA treatment, of whom 92 and 64 received STD and HD ibuprofen, respectively. Baseline characteristics were mostly similar (Table 1), with the exception that HD neonates were older (16 [±8] vs. 14 [±9] days, p< 0.01), had larger PDA diameter (2.4 [±0.5] vs. 2.1 [0.5] mm, p< 0.01) and were less likely to be mechanically ventilated (63% vs. 81%, p=0.02) at the time of treatment. On multivariable analysis, there was no difference in the frequency of PDA closure (32% vs. 30%, aOR 1.03, 95% CI: 0.45, 2.34), or surgical closure (aOR 1.44, 95% CI: 0.55, 3.76). Neonatal outcomes were similar, including a composite of death or major morbidity (aOR 1.34, 95% CI: 0.89, 2.02) (Table 2). Neonates treated with HD were definitively extubated earlier (aHR 1.93, 95% CI: 1.11, 2.34).

Conclusion(s): HD ibuprofen was no more effective than STD ibuprofen for late PDA treatment among ELGANs. Overall therapeutic effectiveness was low, indicating a need to identify novel, effective treatment approaches for PDA among ELGANs.